3-Loweralkylcarbamylsulfonamido-4-phenylaminopyridine-N-oxides, derivatives thereof and pharmaceutical compositions containing same

ABSTRACT

This invention relates to new derivatives of pyridine having anti-inflammatory and diuretic properties. 
     The new derivatives of pyridine may be represented by the following general formula: ##STR1## in which X represents an amino, C 1  -C 4  -alkylamino, oxy or thio group, R 1  represents a group of the formula R 3  NHCA (II), wherein A represents oxygen or sulfur, and R 3  represents a C 1  -C 4  -alkyl, alkenyl, cycloalkyl, phenyl (which may be substituted) or R 4  CO (III) group, R 4  representing a phenyl group (which may be substituted), R 2  represents hydrogen or a C 1  -C 4  alkyl group and Z represents a C 1  -C 4  -alkyl, methylfuryl, pyridyl or phenyl group (which may be substituted). 
     This invention relates also to the N-oxides of the compounds of formula I, as well as to the acid and base addition salts of said compounds.

BRIEF DESCRIPTION OF THE INVENTION

This invention relates to new derivatives of pyridine, their preparationand use.

The new derivatives of pyridine are of the following general formula:##STR2## in which

X represents an amino, C₁ -C₄ -alkylamino, oxy or thio group;

R₁ represents a group of the formula:

    R.sub.3 NHCA                                               (II),

wherein A represents oxygen or sulfur and R₃ represents a C₁ -C₄ -alkyl,alkenyl, cycloalkyl or phenyl group, the latter being possiblysubstituted, or a group of the formula R₄ CO (III), wherein R₄represents a phenyl group which may be substituted;

R₂ represents hydrogen or a C₁ -C₄ -alkyl group, and

Z represents a C₁ -C₄ -alkyl, methylfuryl, pyridyl or phenyl group, thephenyl group being possibly substituted by one or more substituentsselected from the C₁ -C₄ -alkyl, alkoxy, halo, trifluoromethyl, nitrogroups, with the provisos that:

1. when X represents an amino group, Z, R₁, R₂, R₃ and R₄ may have allthe above indicated meanings;

2. when X represents an oxy or thio group, Z may only represent a phenylgroup as defined hereabove;

3. when X represents an alkylamino group, Z may only represent a C₁ -C₄-alkyl group or a phenyl group as defined hereabove and R₁ may furtherrepresent a group of the formula:

    R.sub.5 CO                                                 (IV),

in which R₅ represents hydrogen or a C₁ -C₄ -alkyl group;

4. when X represents an amino group and Z is other than a phenyl group,or when X represents an oxy or thio group, R₁ may further representhydrogen or a group of the formula (IV) as above defined.

When, in the compounds of formula I, X represents an imino group, Z aphenyl group and R₁ a group of formula III, this invention relates tothe cyclization products of the formula: ##STR3## in which R₂ and R₄have the above meanings, said cyclization products being obtainedspontaneously together with the compounds of formula I, in which X, Zand R₁ have the meanings given in this paragraph.

The invention also relates to the N-oxides of the compounds of formula Iin which the oxygen atom is attached to the nitrogen atom of thepyridin, and to the base and acid addition salts of said compounds offormulae I and V.

DETAILED DESCRIPTION OF THE INVENTION

The compounds according to this invention, i.e. the compounds offormulae I and V, may be prepared by various processes:

FIRST PROCESS

When it is desired to obtain a compound of formula I, wherein R₁represents a R₃ NHCA group as defined above, the process comprisesreacting a compound of the following formula: ##STR4## with anisocyanate or isothiocyanate of the formula:

    R.sub.3 N = C = A                                          (VII),

in which Z, R₂, R₃ and A have the above meanings.

SECOND PROCESS

When it is desired to obtain a compound of formula I, wherein R₁represents a R₃ NHCO group as defined above, the process comprisesreacting a compound of formula VI with an alkylhaloformate of theformula: ##STR5## in which R₇ represents a C₁ -C₄ -alkyl group and Halrepresents an halogen atom, and an amine of the formula:

    R.sub.3 NH.sub.2                                           (IX),

in which R₃ has the above meanings.

THIRD PROCESS

When it is desired to obtain a compound of formula I, wherein R₁represents a R₃ NHCA group as defined above and X represents an imino oralkylimino group, the process comprises reacting a compound of theformula: ##STR6## with an amine of the formula:

    R.sub.8 -- NH -- Z                                         (XI),

wherein R₈ represents hydrogen or a C₁ -C₄ -alkyl group, R₂, Hal, R₃ andZ having the above meanings.

FOURTH PROCESS

When it is desired to obtain a compound of formula I, wherein Zrepresents a phenyl group which may be substituted in the manner definedabove, R₁ represents hydrogen or a R₃ NHCA group as above defined or aR₄ CO or R₅ CO group as above defined and X represents a thio or oxygroup, the process comprises reacting a compound of the formula:##STR7## with a phenolate or thiophenolate of the formula:

    Na -- X -- Z                                               (XIII).

fifth process

when it is desired to obtain a compound of formula I, wherein R₁represents a R₄ CO or R₅ CO group as defined above, or a compound offormula V, the process comprises reacting a compound of VI with ananhydride of an alkane-carboxylic acid of the formula:

    (R.sub.4 --CO).sub.2 O or (R.sub.5 --CO).sub.2 O           (XIV)

or with a chloride of an alkane-carboxylic acid of the formula:

    R.sub.4 COCl or R.sub.5 COCl                               (XV).

sixth process

when it is desired to obtain a compound of formula I, in which X, Z andR₂ have the above meanings and R₁ represents R₃ NHCO, the processcomprises heating a compound of formula I, in which R₁ represents a R₃NHCS group, in an aqueous-alcoholic solution of sodium carbonate with anexcess of HgO.

SEVENTH PROCESS

When it is desired to obtain the N-oxides of the compounds of formula I,the above processes are applied, except that the corresponding N-oxidesof the starting pyridine derivatives are used.

EIGHTH PROCESS

When it is desired to obtain the N-oxides of the compounds of formula I,the process comprises treating a compound of formula I withmeta-chloroperoxy-benzoic acid.

The compounds of formula VI, which are used as starting material in thefirst and sixth processes, may be prepared by the fourth above-describedprocess or by reacting an aliphatic amine with a 4-halogeno-pyridinesulfonamide according to the third above-described process.

It has been found that the compounds of formulae I and V haveanti-inflammatory and diuretic properties.

These properties have been determined by the following tests.

1. Pharmacological test for anti-inflammatory properties

The compounds to be tested are given as freshly prepared solutions orsuspensions by oral route 1 hour before injecting the paw of rats withcarrageenan which is a known inflammatory agent.

The inflammatory agent (carrageenan) either in solution or suspension isthen injected into the plantar tissue of the right hind paw of each rat,the left paw remaining untreated and serving as control. Each animalreceives, for example, 0.05 ml of an aqueous solution containing 1 % byweight of carrageenan and 0.9 % of sodium chloride.

4 hours after the injection of the inflammatory agent, the importance ofswelling is determined by plethysmography and is expressed as a percentof the volume of the control paw.

The anti-inflammatory effect expressed as a percentage of inhibition isobtained by comparison between rats treated with the anti-inflammatorycompound and a control group of rats.

2. Pharmacological tests for diuretic properties

Lots of 3 rats weighting 250-300 g have been constituted at random, eachof them being submitted to the same treatment.

The compound to be tested was administered by gastric gavage at a doseof 50 ml/kg as a solution or a suspension in water containing 0.45 % ofmethylcellulose (which is an inert mucilaginous substance). Controlanimals received only distilled water as a placebo. At the same time,all the animals received 25 ml/kg of physiological saline bysubcutaneous injection.

The rats were then placed in metabolic cages, each cage containing 3animals receiving the same treatment. The urines have been collectedduring 4 hours.

The increase of urine volume in the treated animals compared with theurine volume of the control animals shows the diuretic action. Thediuresis is expressed in ml/kg of body weight.

The results of the tests made with a great number of compounds accordingto this invention are given in the following table.

                  TABLE                                                           ______________________________________                                        Compounds        Pharmacological properties                                   Code   Exam-         Diuresis    % inhibition                                 Number ple           ml/kg       of acute oedema                              ______________________________________                                        C 2129 11            30.3        23.2                                         JDL 181                                                                              77            14.8        21.6                                         344    1             66.9        82.4                                         346    11(+)         15.3        53.6                                         355    2             57.0        48.8                                         356    22            54.7        80.8                                         357    24            11.2        52.0                                         358    5             17.9        57.3                                         360    6             5.2         33.6                                         361    7             9.6         56.8                                         362    8             8.1         37.6                                         363    14            40.1        63.2                                         364    3             37.7        58.4                                         365    10            8.7         43.2                                         366    9             11.1        56.0                                         367    23            11.1        80.0                                         368    4             6.1         57.0                                         375    36            80.5        46.4                                         378    19            84.0        74.4                                         379    34            76.5        63.2                                         383    18            57.8        55.2                                         384    85            12.8        66.4                                         385    86            17.6        45.6                                         386    20            80.5        80.8                                         387    35            80.9        76.8                                         388    38            37.0        66.4                                         389    39            73.3        64.0                                         390    40            16.9        47.2                                         391    41            9.6         74.4                                         402    27            65.4        76.8                                         403    28            74.9        76.8                                         404    29            43.1        76.8                                         413    37            92.5        76.8                                         414    21            82.9        75.2                                         415    47            47.0        75.2                                         416    48            52.8        85.6                                         417    49            58.3        72.8                                         420    26            65.0        52.8                                         421    30            72.0        88.8                                         422    31            56.7        46.4                                         423    50            68.7        64.0                                         424    51            21.0        50.4                                         425    52            37.7        42.4                                         426    53            22.0        73.6                                         427    32            11.4        53.6                                         428    33            15.6        17.6                                         463    70            76.1        73.6                                         464    71            81.6        76.8                                         465    58            76.7        71.2                                         466    59            70.7        68.0                                         467    55            65.8        69.6                                         468    56            77.2        72.0                                         469    67            46.9        60.8                                         470    68            74.9        83.2                                         471    78            37.7        70.4                                         472    79            69.6        54.4                                         473    62            24.0        41.6                                         474    63            33.3        --                                           475    60            34.3        79.2                                         476    61            42.1        92.0                                         477    44            43.6        61.6                                         478    45            29.7        29.6                                         479    46            44.3        45.6                                         480    12            26.4        65.6                                         482    14            25.3        0                                            483    83            12.4        0                                            484    82            9.0         13.6                                         485    80            51.3        15.2                                         486    76            3.6         16.8                                         487    75            10.5        20.8                                         488    74            16.4        24.8                                         491    84            25.1        88.0                                         492    15            14.9        88.8                                         493    66            50.7        59.2                                         494    69            75.9        85.6                                         495    57            76.3        66.2                                         496    54            72.1        70.4                                         501                  35.9        39.2                                         502    16            43.8        1.6                                          503    43            48.9        71.2                                         504    64            17.2        43.0                                         505    65            56.3        68.0                                         506    81            13.5        --                                           509    25            106.4       --                                           510    16(+)         92.5        --                                           511    72            66.4        72.0                                         512    73            65.9        78.7                                         ______________________________________                                         (+)=N-oxide.                                                             

This invention relates therefore also to pharmaceutical compositionscontaining as active ingredient at least one compound of the formula Ior V, or a N-oxide or such a compound or a base- or acid-addition saltthereof, together with a pharmaceutically acceptable vehicle or carrier.

The compounds of this invention may be administered in the form ofdragees, tablets, capsules and suppositories at daily doses of 50 to 300mg of active compound.

EXAMPLES

The following examples illustrate the preparation of compounds offormulae I and V.

EXAMPLE 1 Preparation of3-butylcarbamylsulfonamido-4-(3'-chloro)-phenylaminopyridine (formula I: Z = 1-chlorophenyl; R₁ = CONHC₄ H₉ ; R₂ = H and X = NH). A. FIRSTPROCESS

3-sulfonamido-4-(3'-chloro)-phenylaminopyridine (0.02 mole) is reactedwith n-butylisocyanate (0.025 mole) in the presence of 1 to 2 ml oftriethylamine by heating at 85°-95° C during 10 hours. The residue istaken up with alcohol (30 ml) and NaOH 2N, acidified by means of aceticacid and then diluted with an excess of water which gives a precipitate.The mixture is treated with a 5 % solution of sodium bicarbonate in amixture (3:1) of water and alcohol during 1 hour, then filtered andacidified, whereby the desired product precipitates.

B. SECOND PROCESS

The same product is obtained by reacting in acetone a mixture of ethylchloroformate (0.06 mole),3-sulfonamido-4-(3'-chloro)-phenylaminopyridine (0.05 mole) andpotassium carbonate (8.5 g), by reflux heating with stirring for 2hours. The acetone is distilled off and the residue is poured into anexcess of water which is acidified by means of hydrochloric acid. Theproduct which appears is extracted with ether, the ether is dried andthen distilled to give a residue which is dissolved in diethoxyethane orpropylene glycol (10 ml), to which butyl-amine (0.02 mole) is added, theresulting mixture being reflux heated during 15 hours, diluted with 100ml of water and acidified by means of acetic acid. After precipitation,the product is purified with sodium bicarbonate and recovered asdescribed in part A of this example.

C. THIRD PROCESS

3-butylcarbamylsulfonamido-4-chloropyridine (0.01 mole) andmetachloroaniline (0.0125 mole) and copper powder are mixed intimatelyand heated carefully until the temperature spontaneously rises. Theresulting reaction mixture is cooled and the product is purified andisolated as in part A of this example.

Whenever prepared by one of the above described methods, the product isin the form of white crystals, m.p. 139°-140° C.

EXAMPLE 2 Preparation of3-propylcarbamylsulfonamido-4-(3'-trifluoromethyl)-phenylaminopyridine(formula I : Z = trifluoromethylphenyl; R₁ = CONHC₃ H₇ ; R₂ = H and X =NH).

This product is prepared by the methods described in parts A and C ofExample 1, using each time the appropriate starting materials. Whitecrystals; m.p. 166°-168° C.

EXAMPLE 3 Preparation of3-cyclohexylcarbamylsulfonamido-4-(3'-trifluoromethyl)-phenylaminopyridine(formula I : Z = trifluoromethylphenyl; R₁ = CONHC₆ H₁₁ ; R₂ = H and X =NH).

This product is prepared by the methods described in parts A and C ofExample 1, using each time the appropriate starting materials. Whitecrystals; m.p. 126°-128° C.

EXAMPLE 4 Preparation of3-phenylcarbamylsulfonamido-4-(3'-trifluoromethyl)-phenylaminopyridine(formula I : Z = trifluoromethylphenyl; ##STR8## R₂ = H and X = NH).

Using the method described in part A of Example 1, one obtains whitecrystals; m.p. 180°-182° C.

EXAMPLE 5 Preparation of3-propionylsulfonamido-4-(N-methylanilino)-pyridine (formula I : Z =phenyl; R₁ = COC₂ H₅ ; R₂ = H and X = N--CH₃).

The following mixture:

0.01 mole of 3-sulfonamido-4-(N-methylanilino)-pyridine

10 ml of propionyl chloride or anhydride

10 ml of pyridine is reacted during 12 hours (fifth process).

The reacted mixture is poured into an excess of 10 % NaOH, filteredwhenever necessary and acidified by means of acetic acid which gives aprecipitate. The precipitate is dissolved in 100 ml of 5 % sodiumbicarbonate in a mixture of water and alcohol (3:1). The mixture thusobtained is filtered and the filtrate is acidified to give the desiredproduct as a yellowish white product; m.p. 247° C.

EXAMPLE 6 Preparation of 3-sulfonamido-4-(3'-chloro)-phenoxypyridine(formula I : Z = chlorophenyl; R₁ = H; R₂ = H and X = O).

Fourth process -- a mixture of 3-sulfonamido-4-chloropyridine (0.02mole), sodium meta-chlorophenolate (0.04 mole) and meta-chlorophenol(0.02 mole) is heated and maintained at about 160°-180° C during 1/2hour. The mixture is taken up with 100 ml of alcohol, acidified by meansof acetic acid and diluted with water. The desired product precipitates;m.p. 161°-163° C (white crystals).

EXAMPLE 7 Preparation of 3-sulfonamido-4-(3'-chloro)-thiophenoxypyridine(formula I : Z = chlorophenyl; R₁ = H; R₂ = H and X = S).

Fourth process -- the following mixture is allowed to boil during 1 hour: 0.02 mole of 3-sulfonamido-4-chloropyridine and 0.03 mole of sodiummetachlorothiophenolate. The mixture is diluted with an excess of waterand acidified with acetic acid. The product crystallizes as whitecrystals; m.p. 150°-152° C.

EXAMPLE 8 Preparation of3-acetylsulfonamido-4-(3-chloro)-thiophenoxy-pyridine (formula I : Z =chlorophenyl; R₁ = COCH₃ ; R₂ = H and X = S). A. FIFTH PROCESS

3-sulfonamido-4-(3'-chloro)-thiophenoxypyridine (5 g) is contacted withpyridine (25 ml) and acetic anhydride (25 ml) during 3 hours. Thereacted mixture is poured into an excess of 10 % NaOH, filtered ifnecessary and acidified by means of acetic acid. The product isseparated, purified by dissolution in 200 ml of 5 % NaHCO₃ in a mixtureof water and alcohol (3:1) and again precipitated by means of aceticacid.

B. FOURTH PROCESS

3-acetylsulfonamido-4-chloropyridine (0.01 mole) and sodiummetachlorothiophenolate (0.01 mole) and absolute ethanol (100 ml) arereflux heated during 1 hour. After distillation of 50 ml of ethanol, themixture is diluted with an excess of water, giving a precipitate whichis purified and isolated as in part A of this example. White product;m.p. 229°-230° C.

EXAMPLE 9 Preparation of3-butylcarbamylsulfonamido-4-(3'-chloro)-thiophenoxypyridine (formula I: Z = chlorophenyl; R₁ = CONHC₄ H₉ ; R₂ = H and X = S).

A. The desired product is obtained from3-sulfonamido-4-(3'-chloro)-thiophenoxypyridine as described in part Aof Example 1.

B. The same product is also obtained by the fourth process using sodiummetachlorothiophenolate and absolute ethanol as a diluent.

In both instances, one obtains a white product; m.p. 195°-197° C.

EXAMPLE 10 Preparation of3-propylcarbamylsulfonamido-4-(3'-chloro)-phenoxypyridine (formula I : Z= chlorophenyl; R₁ = CONHC₃ H₇ ; R₂ = H and X = O).

First process -- 3-sulfonamido-4-(3'-chloro)-phenoxypyridine (0.01 mole)is intimately mixed with propylisocyanate (0.0125 mole) andtriethylamine (0.5-1 ml). The mixture thus obtained is maintained 4hours at 85°-95° C, taken up with 50 ml of alcohol and a few ml of NaOH2N, heated to dissolve any soluble matter, acidified with acetic acid.300 ml of water are then added thereto. The product is purified andisolated as described previously, using a solution of NaHCO₃ to givesmall white crystals; m.p. 177°-179° C.

EXAMPLE 11 Preparation of3-benzoylsulfonamido-4-(3'-trifluoromethyl)-phenylaminopyridine and3-phenyl-4-metatrifluoromethyl-4H-pyridino-[4,3-e]-1,2,4-thiadiazine-1,1-dioxide(formulae I and V : Z = trifluoromethyl-phenyl; ##STR9## R₂ = H; R₄ =phenyl and X = NH).

A. 0.01 mole of 3-sulfonamido-4-(3-trifluoromethyl)-phenylaminopyridine,0.030 mole of benzoyl chloride and 20 ml of anhydrous pyridine are leftin contact with one another for 24 hours. The resulting mixture ispoured into NaOH (10 %). One obtains a precipitate of the cyclizedsecond title product (m.p. 290° C) and a solution. When neutralized byacetic acid, the solution gives a precipitate of impure first titlecompound. Said precipitate is stirred with an aqueous solution of NaHCO₃to extract the little amount of benzoic acid contained therein. It isthen treated with a water-alcohol solution of NaHCO₃, dissolved, theresulting solution is filtered and neutralized by means of acetic acid.The desired first title compound precipitates (m.p. 249° C). Bytreatment with a dehydrating agent, such as acetic anhydride, the firsttitle compound is converted into the second title compound.

B. A mixture of 0.01 mole of 4-chloro-3-benzoylsulfonamido-pyridine,0.01 mole of meta-trifluoromethylaniline and a little amount of copperpowder is heated at about 80° C. A spontaneous heating occurs. Themixture is maintained during 10 minutes at about 80°-100° C and is thentaken up with water and adjusted to a pH of 5. The precipitate istreated as described in part A of this example, using a water-alcoholicsolution of sodium bicarbonate, filtered and neutralized by means ofacetic acid. The first title compound crystallizes (m.p. 249° C). Bytreatment of this compound using acetic anhydride, the first titlecompound cyclizes to form the second title compound (m.p. 290° C).

EXAMPLE 12 Preparation of3-allyl-thiocarbamyl-sulfonamido-4-(3'-chloro)-phenylaminopyridine(formula I : Z = chlorophenyl; R₁ = allyl-thiocarbamyl; R₂ = H and X =NH).

In a mixture of equal parts of water and dioxane, 0.01 mole of sodiumsalt of 3-sulfonamido-4-(3'-chloro)-phenylaminopyridine is dissolved and0.02 mole of allylisothiocyanate is added little by little.

The reaction mixture is maintained 1 hour at 50° C under stirring, thendiluted by 250 ml of water and acidified.

The crude product is purified by dissolution in a water-alcohol solutionof NaHCO₃ and back-precipitation by means of acetic acid; (m.p.175°-177° C).

EXAMPLE 13 Preparation of3-allylcarbamylsulfonamido-4-(3'-chloro)-phenylaminopyridine (formula I: Z = chlorophenyl; R₁ = allylcarbamyl; R₂ = H; X = NH). SIXTH PROCESS

0.01 mole of3-allylthiocarbamylsulfonamido-4-(3'-chloro)-phenylaminopyridine isdissolved in 100 ml of water and 5 g of Na₂ CO₃. One adds 10 g of HgOand one heats and maintains the reaction mixture under reflux conditionsuntil all the sulphur is removed as HgS. Said mixture is filtrated andits pH is adjusted to 4-5. The product precipitates. It is purified bydissolution in NaHCO₃ and back precipitation (m.p. 161°-163° C).

EXAMPLE 14 Preparation of3-isopropylcarbamylsulfonamido-4-isopropyl-aminopyridine (formula I : Z= isopropyl; R₁ = isopropylcarbamyl; R₂ = H and X = NH).

By reacting the appropriate products as described in any of examples 1A,B or C, one obtains the desired title compound.

When applying the process of Example 1C, the reactants are preferablyheated to 120° C in a closed reaction vessel. Alternatively, anintermediate solvent such as propyleneglycol is used (m.p. 193° C).

EXAMPLE 15 Preparation of3-methylcarbamylsulfonamido-4-methyl-furyl-aminopyridine (formula I : Z= methylfuryl; R₁ = methylcarbamyl; R₂ = H and X = NH).

This product is conveniently prepared by applying any of the processesdescribed in Examples 1A and 1C with very good results; m.p. 208°-209°C.

EXAMPLE 16 Preparation of3-isopropylcarbamylsulfonamido-4-(3'-methyl)-phenylaminopyridine-N-oxide(formula I : Z = methylphenyl; R₁ = isopropylcarbamyl; X = NH). 1.SEVENTH PROCESS

4-chlorosulfonamidopyridine-N-oxide (m.p. 217°-219° C) is firstcondensed with toluidine using the usual method. 0.01 mole of the3-sulfonamido-4-(3'-methyl)-phenylaminopyridine-N-oxide thus obtained isreacted, in the form of its sodium salt, with 0.011 mole ofisopropylisocyanate in 50 ml of a (1:1) water-dioxane mixture for 1 hourat about 40° C. The mixture is diluted with 250 ml of water and adjustedto pH 4-5. The crude product is purified by dissolution in awater-alcohol (3:1) solution of NaHCO₃ and back precipitation by meansof HOAC.

2. EIGHTH PROCESS

0.01 mole of3-isopropylcarbamylsulfonamido-4-(3'-methyl)-phenylaminopyridine isdissolved in 150 ml of CHCl₃. 0.01 mole of metachloroperoxybenzoic acidis slowly added drop by drop under good stirring and the reaction isallowed to proceed for a few hours under cool conditions. CHCl₃ isevaporated and the residue is taken up with ether. The insoluble matter,mainly consisting of the crude product, is purified by the usual NaHCO₃treatment; (m.p. 158° C).

EXAMPLE 17 Preparation of3-ethylcarbamylsulfonamido-4-(3'-chloro)-phenylamino-5-methylpyridine(formula I : Z = chlorophenyl; R₁ = ethylcarbamyl; R₂ = methyl; X = NH).(m.p. 182° C).

This compound is obtained by any one of the methods described inExample 1. It is however preferred to apply the method of Example 1Ausing as starting materials ethyl isocyanate and3-sulfonamido-4-(3'-chloro)-phenylamino-5-methylpyridine (m.p. 251° C).

EXAMPLES 18-92

Applying any of the above-described methods, the following compoundslisted in the table hereinafter are prepared. Unless otherwisespecified, all these products are white crystals, sparingly soluble inwater, more soluble in alcohol and acetone, soluble in the bases exceptthe second title compound of Example 11, and concentrated inorganicacids.

    ______________________________________                                        Com-                                                                          pounds                                                                        of Ex.                                                                              Code N°                                                                         Name and melting point of compound                             ______________________________________                                        18    JDL 383  3-propylcarbamylsulfonamido-4-N-                                              methyl-anilinopyridine (formula I :                                           Z = phenyl ; R.sub.1 = propylcarbamyl;                                        R.sub.2 = H and X = NCH.sub.3); m.p. 105-107° C         19    JDL 378  3-methylcarbamylsulfonamido-4-(3'-                                            trifluoromethyl)-phenylaminopyrid-                                            ine (formula I : Z = trifluoro-                                               methylphenyl; R.sub.1 = methylcarbamyl;                                       R.sub.2 = H and X = NH); m.p. 189-191° C                20    JDL 386  3-ethylcarbamylsulfonamido-4-(3'-                                             trifluoromethyl)-phenylaminopyrid-                                            ine (formula I : Z = trifluorome-                                             thylphenyl ; R.sub.1 = ethylcarbamyl;                                         R.sub.2 = H and X = NH); m.p. 164-165° C.               21    JDL 414  3-isopropylcarbamylsulfonamido-4-                                             (3'-trifluoromethyl)-phenylamino-                                             pyridine (formula I : Z = trifluoro-                                          methylphenyl; R.sub.1 = isopropylcarb-                                        amyl; R.sub.2 = H and X = NH); m.p. 177° C              22    JDL 356  3-butylcarbamylsulfonamido-4-(3'-                                             trifluoromethyl)-phenylaminopyrid-                                            ine (formula I : Z = trifluorometh-                                           ylphenyl; R.sub.1 = butylcarbamyl;                                            R.sub.2 = H and X = NH); m.p. 150-152° C                23    JDL 367  3-tertiobutylcarbamylsulfonamido-4-                                           (3'-trifluoromethyl)-phenylamino-                                             pyridine (formula I : Z = trifluoro-                                          methylphenyl; R.sub.1 = t-butylcarbamyl;                                      R.sub.2 = H and X = NH); m.p. 168-170° C                24    JDL 357  3-parachlorophenylcarbamylsulfon-                                             amido-4-(3'-trifluoromethyl)-                                                 phenylaminopyridine (formula I :                                              Z = trifluoromethylphenyl; R.sub.1 =                                          para-chlorophenylcarbamyl; R.sub.2 = H                                        and X = NH); m.p. 208-210° C                            25    JDL 509  3-ethylcarbamylsulfonamido-4-(3'-                                             trifluoromethyl)-phenylaminopyrid-                                            ine-N-oxide (formula I : Z = tri-                                             fluoromethylphenyl; R.sub.1 = ethylcarb-                                      amyl; R.sub.2 = H and X = NH); m.p. 163° C              26    JDL 420  3-ethylthiocarbamylsulfonamido-4-                                             (3'-trifluoromethyl)-phenylamino-                                             pyridine (formula I : Z = trifluoro-                                          methylphenyl; R.sub.1 = ethylthiocarba-                                       myl; R.sub.2 = H and X = NH); m.p. 178-                                       180° C                                                  27    JDL 402  3-methylcarbamylsulfonamido-4-(2'-                                            chloro)-phenylaminopyridine (formu-                                           la I : Z = chlorophenyl; R.sub.1 = methyl-                                    carbamyl; R.sub.2 = H and X = NH); m.p.                                       192° C                                                  28    JDL 403  3-ethylcarbamylsulfonamido-4-(2'-                                             chloro)-phenylaminopyridine (formu-                                           la I : Z = chlorophenyl; R.sub.1 =                                            ethylcarbamyl; R.sub.2 = H and X = NH);                                       m.p. 176-178° C                                         29    JDL 404  3-propylcarbamylsulfonamido-4-(2'-                                            chloro)-phenylaminopyridine (formu-                                           La I : Z = chlorophenyl; R.sub.1 =                                            propylcarbamyl; R.sub.2 = H and X = NH);                                      m.p. 151-152° C                                         30    JDL 421  3-isopropylcarbamylsulfonamido-4-(2'-                                         chloro)-phenylaminopyridine (formu-                                           la I : Z = chlorophenyl; R.sub.1 = iso-                                       propylcarbamyl; R.sub.2 =  H and X = NH);                                     m.p. 144° C                                             31    JDL 422  3-butylcarbamylsulfonamido-4-(2'-                                             chloro)-phenylaminopyridine (for-                                             mula I : Z = chlorophenyl; R.sub.1 =                                          t-butylcarbamyl; R.sub.2 = H and X = NH);                                     m.p. 116° C                                             32    JDL 427  3-tertiobutylcarbamylsulfonamido-                                             4-(2'-chloro)-phenylaminopyridine                                             (formula I : Z = chlorophenyl;                                                R.sub.1 = butylcarbamyl; R.sub.2 = H and                                      X = NH); m.p. 185° C                                    33    JDL 428  3-cyclohexylcarbamylsulfonamido-4-                                            (2'-chloro)-phenylaminopyridine                                               (formula I : Z = chlorophenyl;                                                R.sub.1 = cyclohexylcarbamyl; R.sub.2 = H                                     and X = NH); m.p. 137° C                                34    JDL 379  3-methylcarbamylsulfonamido-4-(3'-                                            chloro)-phenylaminopyridine (formu-                                           la I: Z = chlorophenyl; R.sub.1 =                                             methylcarbamyl; R.sub.2 = H and X = NH);                                      m.p. 174-176° C                                         35    JDL 387  3-ethylcarbamylsulfonamido-4-(3'-                                             chloro)-phenylaminopyridine (for-                                             mula I: Z = chlorophenyl; R.sub.1 =                                           ethylcarbamyl; R.sub.2 = H and X = NH);                                       m.p. 163-165° C                                         36    JDL 375  3-propylcarbamylsulfonamido-4-(3'-                                            chloro)-phenylaminopyridine (formu-                                           la I: Z = chlorophenyl; R.sub.1 =                                             propylcarbamyl; R.sub.2 = H and X = NH);                                      m.p. 176° C                                             37    JDL 413  3-isopropylcarbamylsulfonamido-4-                                             (3'-chloro)-phenylaminopyridine                                               (formula I: Z = chlorophenyl; R.sub.1                                         = isopropylcarbamyl; R.sub.2 = H and                                          X = NH); m.p. 179° C                                    38    JDL 388  3-tertiobutylcarbamylsulfonamido-                                             4-(3'-chloro)-phenylaminopyridine                                             (formula I: Z = chlorophenyl; R.sub.1                                         = t-butylcarbamyl; R.sub.2 = H; X = NH);                                      m.p. 172-173° C                                         39    JDL 389  3-cyclohexylcarbamylsulfonamido-4-                                            (3'-chloro)-phenylaminopyridine                                               (formula I: Z = chlorophenyl;                                                 R.sub.1 = cyclohexylcarbamyl; R.sub.2 = H                                     and X = NH); m.p. 125° C                                40    JDL 390  3-phenylcarbamylsulfonamido-4-(3'-                                            chloro)-penylaminopyridine (formu-                                            la I: Z = chlorophenyl; R.sub.1 = phe-                                        nylcarbamyl; R.sub.2 = H and X = NH);                                         m.p. 214° C                                             41    JDL 391  3-parachlorophenylcarbamylsulfon-                                             amido-4-(3'-chloro)-phenylamino-                                              pyridine (formula I: Z = chloro-                                              phenyl; R.sub.1 = parachlorophenylcarb-                                       amyl; R.sub.2 = H and X = NH); m.p.                                           213-215° C                                              42    JDL 501  3-methylcarbamylsulfonamido-4-(3'-                                            chloro)-phenylamino-5-methylpyrid-                                            ine (formula I: Z = chlorophenyl;                                             R.sub.1 = methylcarbamyl; R.sub.2 = CH.sub.3 and                              X = NH); m.p. 189° C                                    43    JDL 503  3-isopropylcarbamylsulfonamido-4-                                             (3'-chloro)-phenylamino-5-methyl-                                             pyridine (formula I: Z = chloro-                                              phenyl; R.sub.1 = isopropylcarbamyl;                                          R.sub.2 = CH.sub.3 and X = NH); m.p. 174° C             44    JDL 477  3-methylthiocarbamylsulfonamido-4-                                            (3'-chloro)-phenylaminopyridine                                               (formula I: Z = chlorophenyl; R.sub.1                                         = methylthiocarbamyl; R.sub.2 = H and                                         X = NH); m.p. 194-195° C                                45    JDL 478  3-ethylthiocarbamylsulfonamido-4-                                             (3'-chloro)-phenylaminopyridine                                               (formula I: Z = chlorophenyl;                                                 R.sub.1 = ethylthiocarbamyl; R.sub.2 = H                                      and X = NH); m.p. 195-196° C                            46    JDL 479  3-isopropylthiocarbamylsulfonamido-                                           4-(3'-chloro)-phenylaminopyridine                                             (formula I: Z = chlorophenyl;                                                 R.sub. 1 = isopropylthiocarbamyl; R.sub.2 = H                                 and X = NH); m.p. 189-191° C                            47    JDL 415  3-methylcarbamylsulfonamido-4-(4'-                                            chloro)-phenylaminopyridine (formu-                                           la I: Z = chlorophenyl; R.sub.1 = meth-                                       ylcarbamyl; R.sub.2 = H and X = NH);                                          m.p. 180° C                                             48    JDL 416  3-ethylcarbamylsulfonamido-4-(4'-                                             chloro)-phenylaminopyridine (formu-                                           la I: Z = chlorophenyl; R.sub.1 =                                             ethylcarbamyl; R.sub.2 = H and X = NH);                                       m.p. 201° C                                             49    JDL 417  3-propylcarbamylsulfonamido-4-(4'-                                            chloro)-phenylaminopyridine (for-                                             mula I: Z = chlorophenyl; R.sub.1  =                                          propylcarbamyl; R.sub.2 = H and X =                                           NH); m.p. 168-170° C                                    50    JDL 423  3-isopropylcarbamylsulfonamido-4-                                             (4'-chloro)-phenylaminopyridine                                               (formula I: Z = chlorophenyl;                                                 R.sub.1 = isopropylcarbamyl; R.sub.2 = H                                      and X = NH); m.p. 143° C                                51    JDL 424  3-butylcarbamylsulfonamido-4-(4'-                                             chloro)-phenylaminopyridine (for-                                             mula I: Z = chlorophenyl; R.sub.1 =                                           butylcarbamyl; R.sub.2 = H and X = NH);                                       m.p. 170-172° C                                         52    JDL 425  3-tertiobutylcarbamylsulfonamido-4-                                           (4'-chloro)-phenylaminopyridine                                               (formula I: Z = chlorophenyl;                                                 R.sub.1 = t-butylcarbamyl; R.sub.2 = H and -  X = NH);                        m.p. 118° C                                             53    JDL 426  3-cyclohexylcarbamylsulfonamido-4-                                            (4'-chloro)-phenylaminopyridine                                               (formula I: Z = chlorophenyl;                                                 R.sub.1 = cyclohexylcarbamyl; R.sub.2 = H                                     and X = NH); m.p. 178° C                                54    JDL 496  3-methylcarbamylsulfonamido-4-(3'-                                            bromo)-phenylaminopyridine (formu-                                            la I: Z = bromophenyl; R.sub.1 = meth-                                        ylcarbamyl; R.sub.2 = H and X = NH);                                          m.p. 187° C                                             55    JDL 467  3-ethylcarbamylsulfonamido-4-(3'-                                             bromo)-phenylaminopyridine (formu-                                            la I: Z = bromophenyl; R.sub.1 = ethyl-                                       carbamyl; R.sub.2 = H and X = NH);                                            m.p. 165-167° C                                         56    JDL 468  3-isopropylcarbamylsulfonamido-4-                                             (3'-bromo)-phenylaminopyridine                                                (formula I: Z = bromophenyl;                                                  R.sub.1 = isopropylcarbamyl; R.sub.2 = H                                      and X = NH); m.p. 157-159° C                            57    JDL 495  3-methylcarbamylsulfonamido-4-(3'-                                            fluoro)-phenylaminopyridine (formu-                                           la I: Z = fluorophenyl; R.sub.1 =                                             methylcarbamyl; R.sub.2 = H and X = NH);                                      m.p. 170-172° C                                         58    JDL 465  3-ethylcarbamylsulfonamido-4-(3'-                                             fluoro)-phenylaminopyridine (formu-                                           la I: Z = fluorophenyl; R.sub.1 = eth-                                        ylcarbamyl; R.sub.2 = H and X = NH);                                          m.p. 158-160° C                                         59    JDL 466  3-isopropylcarbamylsulfonamido-4-                                             (3'-fluoro)-phenylaminopyridine                                               (formula I: Z = fluorophenyl;                                                 R.sub.1 = isopropylcarbamyl; R.sub.2 = H                                      and X = NH); m.p. 163-165° C                            60    JDL 475  3-ethylcarbamylsulfonamido-4-(3',4'-                                          dichloro)-phenylaminopyridine (for-                                           mula I: Z = dichlorophenyl; R.sub.1 =                                         ethylcarbamyl; R.sub.2 = H and X = NH);                                       m.p. 166-168° C                                         61    JDL 476  3-isopropylcarbamylsulfonamido-4-                                             (3',4'-dichloro)-phenylaminopyrid-                                            ine (formula I: Z = dichlorophenyl;                                           R.sub.1 = isopropylcarbamyl; R.sub.2 = H and                                  X = NH); m.p. 123-125° C                                62    JDL 473  3-ethylcarbamylsulfonamido-4-(3',5'-                                          dichloro)-phenylaminopyridine (for-                                           mula I: Z = dichlorophenyl; R.sub.1 =                                         ethylcarbamyl; R.sub.2 = H and X = NH);                                       m.p. 165-167° C                                         63    JDL 474  3-isopropylcarbamylsulfonamido-4-                                             (3',5'-dichloro)-phenylaminopyridine                                          (formula I: Z = dichlorophenyl;                                               R.sub.1 = isopropylcarbamyl; R.sub.2 = H and                                  X = NH); m.p. 124-126° C                                64    JDL 504  3-methylcarbamylsulfonamido-4-(3'-                                            nitro)-phenylaminopyridine (formu-                                            la I: Z = nitrophenyl; R.sub.1 = meth-                                        ylcarbamyl; R.sub.2 = H and X = NH);                                          m.p. 173° C (yellow product)                            65    JDL 505  3-isopropylcarbamylsulfonamido-4-                                             (3'-nitro)-phenylaminopyridine (for-                                          mula I: Z = nitrophenyl; R.sub.1 = iso-                                       propylcarbamyl; R.sub.2 = H and X = NH);                                      m.p. 166° C (yellow product)                            66    JDL 493  3-methylcarbamylsulfonamido-4-(3'-                                            methoxy)-phenylaminopyridine (formu-                                          la I: Z = methoxyphenyl; R.sub.1 =                                            methylcarbamyl; R.sub.2 = H and X =                                           NH); m.p. 177° C                                        67    JDL 469  3-ethylcarbamylsulfonamido-4-(3'-                                             methoxy)-phenylaminopyridine (for-                                            mula I: Z = methoxyphenyl; R.sub.1 =                                          ethylcarbamyl; R.sub.2 = H and X = NH);                                       m.p. 99-101° C                                          68    JDL 470  3-isopropylcarbamylsulfonamido-4-                                             (3'-methoxy)-phenylaminopyridine                                              (formula I: Z = methoxyphenyl;                                                R.sub.1 = isopropylcarbamyl; R.sub.2 = H                                      and X = NH); m.p. 144-146° C                            69    JDL 494  3-methylcarbamylsulfonamido-4-(3'-                                            methyl)-phenylaminopyridine (for-                                             mula I: Z = methylphenyl; R.sub.1 =                                           methylcarbamyl; R.sub.2 = H and X = NH);                                      m.p. 174° C                                             70    JDL 463  3-ethylcarbamylsulfonamido-4-(3'-                                             methyl)-phenylaminopyridine (for-                                             mula I: Z = methylphenyl; R.sub.1 =                                           ethylcarbamyl; R.sub.2 = H and X = NH);                                       m.p. 151-153° C                                         71    JDL 464  3-isopropylcarbamylsulfonamido-4'-                                            (3'-methyl)-phenylaminopyridine                                               (formula I: Z = methylphenyl;                                                 R.sub.1 = isopropylcarbamyl; R.sub.2 =                                        and X = NH); m.p. 163-164° C                            72    JDL 511  3-ethylcarbamylsulfonamido-4-(3'-                                             ethyl)-phenylaminopyridine (formula                                           I: Z = ethylphenyl; R.sub.1 = ethyl-                                          carbamyl; R.sub.2 = H and X =  NH);                                           m.p. 165° C                                             73    JDL 512  3-isopropylcarbamylsulfonamido-4-                                             (3'-ethyl)-phenylaminopyridine                                                (formula I: Z = ethylphenyl; R.sub.1                                          = isopropylcarbamyl; R.sub.2 = H and                                          X = NH); m.p. 145° C                                    74    JDL 488  3-ethylcarbamylsulfonamido-4-(3'-                                             trifluoromethyl-4'-chloro)-phenyl-                                            aminopyridine (formula I: Z = tri-                                            fluoromethyl-chlorophenyl; R.sub.1 =                                          ethylcarbamyl; R.sub.2 = H and X = NH);                                       m.p. 172° C                                             75    JDL 487  3-isopropylcarbamylsulfonamido-4-                                             (3'-trifluoromethyl-4'-chloro)-                                               phenylaminopyridine (formula I:                                               Z = trifluoromethyl-chlorophenyl;                                             R.sub.1 = isopropylcarbamyl; R.sub.2 = H                                      and X = NH); m.p. 178° C                                76    JDL 486  3-butylcarbamylsulfonamido-4-(3'-                                             trifluoromethyl-4'-chloro)-phenyl-                                            aminopyridine (formula I: Z =                                                 trifluoromethyl-chlorophenyl;                                                 R.sub.1 = butylcarbamyl; R.sub.2 = H and                                      X = NH); m.p. 128° C                                    77    JDL 181  3-sulfonamido-4-methylfurylamino-                                             pyridine (formula I: Z = methyl-                                              propyl; R.sub.1 = H; R.sub.2 = H and X =                                      NH); m.p. 160-162° C                                    78    JDL 471  3-ethylcarbamylsulfonamido-4-meth-                                            ylfurylaminopyridine (formula I:                                              Z = methylfuryl; R.sub.1 = ethylcarb-                                         amyl; R.sub.2 = H and X = NH); m.p.                                           183-184° C                                              79    JDL 472  3-isopropylcarbamylsulfonamido-4-                                             methylfurylaminopyridine (formula                                             I: Z = methylfuryl; R.sub.1 = isoprop-                                        ylcarbamyl; R.sub.2 = H and X = NH);                                          m.p. 147-148° C                                         80    JDL 485  3-butylcarbamylsufonamido-4-methyl-                                           furylaminopyridine (formula I: Z =                                            methylfuryl; R.sub.1 = butylcarbamyl;                                         R.sub.2 = H and X = NH); m.p. 159° C                    81    JDL 506  3-methylcarbamylsulfonamido-4-(3'-                                            pyridylamino)-pyridine (formula I:                                            Z = pyridyl; R.sub.1 = methylcarbamyl;                                        R.sub.2 = H and X = NH); m.p. 249° C                    82    JDL 484  3-sulfonamido-4-diethylaminopyrid-                                            ine (formula I: Z = ethyl; R.sub.1 =                                          H; R.sub.2 = H and X = NC.sub.2 H.sub.5); m.p. 171°                    C                                                              83    JDL 483  3-isopropylcarbamylsulfonamido-4-                                             diethylaminopyridine (formula I:                                              Z = ethyl; R.sub.1 = isopropylcarbamyl;                                       R.sub.2 = H and X =  NC.sub.2 H.sub.5); m.p. 102°                      C                                                              84    JDL 491  3-butylcarbamylsulfonamido-4-iso-                                             propylaminopyridine (formula I:                                               Z = isopropyl; R.sub.1 = butylcarbamyl;                                       R.sub.2 = H and X = NH); m.p. 161° C                    85    JDL 384  3-propylcarbamylsulfonamido-4-(3'-                                            chloro)-thiophenoxypyridine (formu-                                           la I: Z = chlorophenyl; R.sub.1 =                                             propylcarbamyl; R.sub.2 = H and X = S);                                       m.p. 174-176° C                                         86    JDL 385  3-tertiobutylcarbamylsulfonamido-                                             4-(3'-chloro)-thiophenoxypyridine                                             (formula I: Z = chlorophenyl; R.sub.1                                         = t-butylcarbamyl; R.sub.2 = H and X =                                        S); m.p. 128° C                                         87    JDL 528  3-sulfonamido-4-metatrifluorometh-                                            yl-thiophenoxypyridine (formula I:                                            Z = metatrifluoromethylphenyl;                                                R.sub.1 =  H; R.sub.2 = H and X = S); m.p.                                    165° C                                                  88    JDL 529  3-butylcarbamylsulfonamido-4-meta-                                            trifluoromethylthiophenoxypyridine                                            (formula I: Z = metatrifluorometh-                                            ylphenyl; R.sub.1 = butylcarbamyl; R.sub.2                                    = H and X = S); m.p. 167-168° C                         89    JDL 530  3-cyclohexylcarbamylsulfonamido-4-                                            metatrifluoromethylthiophenoxypyr-                                            idine (formula I: Z = metatri-                                                fluoromethylphenyl; R.sub.1 = cyclo-                                          hexylcarbamyl; R.sub.2 = H and X = S);                                        m.p. 183-185° C                                         90    JDL 531  3-p-chlorobenzoylsulfonamido-4-                                               metatrifluoromethylthiophenoxy-                                               pyridine (formula I: Z = metatri-                                             fluoromethylphenyl; R.sub.1 = p-chloro-                                       benzoyl; R.sub.2 = H and X = S); m.p.                                         203-205° C                                              91    JDL 532  3-propionylsulfonamido-4-metatri-                                             fluoromethylthiophenoxypyridine                                               (formula I: Z = metatrifluoro-                                                methylphenyl; R.sub.1 = propionyl;                                            R.sub.2 = H and X = S); m.p. 169-171° C                 92    L 2539   3-sulfonamido-4-(2-amino)-thio-                                               phenoxypyridine hydrochloride                                                 (formula I: Z = aminophenyl; R.sub.1                                          = H; R.sub.2 = H and X = S); m.p.                                             238-240° C.                                             ______________________________________                                    

We claim:
 1. A compound of the following formula: ##STR10## in which Xrepresents an amino or C₁ -C₄ -alkylamino group;R₁ represents a group ofthe formula:

    R.sub.3 NHCA                                               (II),

where A represents oxygen or sulfur and R₃ represents a C₁ -C₄ -alkyl,allyl, cyclohexyl, unsubstituted phenyl group or a phenyl groupsubstituted by chloro, or a group of the formula R₄ CO(III), wherein R₄represents an unsubstituted phenyl group or a phenyl group substitutedby chloro; R₂ represents hydrogen or a C₁ -C₄ -alkyl group, and Zrepresents a C₁ -C₄ -alkyl, methylfuryl, pyridyl or unsubstituted phenylgroup, or a phenyl group substituted by one or two halogen atoms or by aC₁ -C₄ -alkyl, alkoxy, trifluoromethyl or nitro group, or by atrifluoromethyl group and a halogen atom with the provisos that:
 1. whenX represents an amino group, Z, R₁, R₂, R₃ and R₄ have all the aboveindicated meanings;2. when X represents an alkylamino group, Z may onlyrepresent a C₁ -C₄ -alkyl group or a phenyl group as defined hereaboveand R₁ may further represent a group of the formula:

    R.sub.5 CO                                                 (IV)

in which R₅ represents hydrogen or a C₁ -C₄ -alkyl group;
 3. when Xrepresents an amino group and Z is other than a phenyl group, R₁ mayfurther represent hydrogen or a group of the formula (IV) as abovedefined,as well as a pyridine N-oxide of the compound of formula I andthe pharmaceutically acceptable base and acid addition salts of saidcompounds. 2.3-Ethylcarbamylsulfonamido-4-(3'-trifluoromethyl)-phenylaminopyridine-N-oxide.3.3-Isopropylcarbamylsulfonamido-4-(3'-methyl)-phenylaminopyridine-N-oxide.4.3-Methylcarbamylsulfonamido-4-(3'-trifluoromethyl)-phenylaminopyridine.5.3-Ethylcarbamylsulfonamido-4-(3'-trifluoromethyl)-phenylaminopyridine.6. 3-Isopropylcarbamylsulfonamido-4-(3'-chloro)-phenylaminopyridine. 7.3-Methylcarbamylsulfonamido-4-(3'-methyl)-phenylaminopyridine.
 8. Apharmaceutical composition containing an anti-inflammatory or diureticeffective amount of a compound of claim 1 and a pharmaceutical carrieror vehicle.